Phase 1, first-in-human, open-label dose escalation and cohort expansion study of KB-0742 in patients with relapsed or refractory solid tumors or non-Hodgkin lymphoma

Cancer Categories

Karmanos Trial ID

NCT ID

Age Group

Scope

Phase

Principal Investigator

Primary Objectives:

Part 1: Dose Escalation

Evaluate the safety and tolerability of
KB-0742 in patients with
relapsed/refractory (R/R) solid tumors or
NHL

Part 2: Cohort Expansion

Further evaluate the safety and tolerability
of KB-0742 in defined patient cohorts

Secondary Objectives:

Part 1: Dose Escalation

Part 2: Cohort Expansion

Further characterize the PK of KB-0742
Further assess preliminary anti-tumor
activity of KB-0742 in defined patient
cohorts

Eligibility

Inclusion Criteria:

Males or females ≥ 18 years old (Parts 1 and 2A); males or females ≥ 12 years old and with a body weight ≥ 40 kg are eligible to enroll with tumor types including soft-tissue sarcomas, Ewing's sarcoma, alveolar rhabdomyosarcoma, NUT midline carcinoma (NMC), or chordoma (Part 2B)
Willing and able to provide consent (and assent for participants between the ages of 12 to <18)
Part 1: Participants who meet at least 1 of the following criteria:

Any R/R solid tumor with, in the opinion of the investigator at the time of screening has at least 1 readily accessible biopsy site(s) and who consents to 1 baseline and 1 on-treatment biopsy. If the feasibility of obtaining biopsies changes after the participant has been consented due to changes in clinical or surgical considerations and the participant otherwise meets all eligibility criteria, they may still enroll/or continue on study.
Tumor type of interest (see list below) with measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) 1.1 or Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) 1.0 for solid tumors or by Lugano Classification or Modified Weighted Assessment Tool (mSWAT) for NHL AND at least 1 measurable scan per one of the above criteria prior to the most recent scan to document the rate of tumor growth before the initiation of study treatment. Tumor types of interest (R/R without other available therapeutic options) are:

SCLC
Epithelial ovarian cancer, TNBC, or NSCLC
Other epithelial solid tumor with evidence of MYC copy number gain based on local testing
Diffuse large B-cell lymphoma with documented MYC translocation or Burkitt's lymphoma (as determined by local testing)
Sarcoma of histologic subtypes known to be associated with transcription factor fusion, specifically: i. Myxoid/round cell sarcoma ii. Clear cell sarcoma iii. Desmoplastic small round cell tumor iv. Low grade fibromyxoid sarcoma v. Extraskeletal myxoid chondrosarcoma vi. Ewing sarcoma vii. Alveolar rhabdomyosarcoma
Chordoma, NUT midline carcinoma, or adenoid cystic carcinoma

Part 2, Cohort A: Participants with histologically or cytologically confirmed solid tumors who have failed, are intolerant to, or are considered ineligible for standard-of-care anti-cancer treatments. Note: Part 2, Cohort A, will include participants with relapsed or refractory solid tumors including NSCLC, TNBC and ovarian cancer.
Part 2, Cohort B: Participants with histologically or cytologically confirmed tumor type of interest without access to or intolerant of other approved therapies, including SCLC.
For both Parts 1 and 2:
Access to a tumor sample for central laboratory testing
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
Evaluable or measurable disease, per RECIST 1.1 or PERCIST 1.0 for solid tumors or the Lugano Classification or mSWAT for NHL
Adequate bone marrow and organ function
Recovery from treatment-related toxicities from prior therapies to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≤ 1 or to baseline level
Must agree to use highly effective birth control during the trial and for at least 3 months after the last dose of study drug; female participants cannot be pregnant or breastfeeding

Exclusion Criteria:

Any other anti-cancer therapies including chemotherapy, immunotherapy, or hormonal therapy within 4 weeks or 5 half-lives (whichever is shorter)
History of surgery (except for diagnostic purposes) or non-palliative radiotherapy within 4 weeks
History of allogeneic transplantation within 6 months
Active central nervous system (CNS) involvement by the underlying malignancy; previously treated CNS metastatic disease is permitted with magnetic resonance imaging (MRI) documentation of stable disease for at least 3 months prior to study start. Participants with SCLC with prior treatment with stereotactic radiosurgery or whole brain radiation therapy for CNS metastatic disease 2 weeks or more before study start may be considered eligible for enrollment if assessed stable and meet all other eligibility criteria.
History of stroke or intracranial hemorrhage within ≤6 months
History of seizure or seizure disorder, ie, recurrent seizures with an underlying etiology and requiring ongoing anti-epileptic medication
Current use of medications associated with seizure risk
Active infections requiring systemic antibiotic, antiviral or antifungal therapy
Known active coronavirus disease 2019 (COVID-19)
Clinically significant heart disease
Uncontrolled hypertension
Prolongation of QT interval at baseline
Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection

Locations

4100 John R
Detroit, MI 48201
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Phone: 800-527-6266

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices